Angiogenesis refers to the growth of new blood vessels, or "neovascularization," and involves the growth of capillaries composed of endothelial cells. Angiogenesis is an integral part of many important biological processes, and may aid in the healing of wounds and fractures, the vascularizing of synthetic skin grafts, and the enhancement of collateral circulation where there has been vascular occlusion or stenosis. New blood vessel formation is required for the development of any new tissue, whether normal or pathological, and thus represents a potential control point in regulating many disease states, as well as a therapeutic opportunity for encouragement of the growth of normal tissue.
The complete process of angiogenesis is not entirely understood, but it is known to involve the endothelial cells of the capillaries. Endothelial cells line the walls of blood vessels, and capillaries are comprised almost entirely of endothelial cells. The angiogenic process comprises a cascade of events, including protease secretion by endothelial cells, degradation of the basement membrane, migration through the surrounding matrix, proliferation, alignment, differentiation into tube-like structures, and synthesis of a new basement membrane.
A number of factors are well-known in the art to stimulate angiogenesis. Many of these are peptide factors, and the most notable among these are fibroblast growth factors, epidermal growth factors, vascular endothelial growth factors, insulin-like growth factors, transforming growth factors, platelet-derived growth factor, and interleukins. Other factors which are known to show angiogenic-stimulating activity, but which are not proteins, include prostaglandins E1 and E2, fragments of hyaluronic acid and nicctinamine. However, the therapeutic applicability of some of these compounds, especially as systemic agents, is limited by their potent pleiotropic effects on various cell types. There remains a need, therefore, for an angiogenic agent with more general applicability.